The cell bodies of neurons that make up the spinothalamic tract are located principally within the dorsal horn of the spinal cord. These neurons receive input from sensory fibers that innervate the skin and internal organs.

The types of sensory information transmitted via the spinothalamic tract are described as affective sensation. This means that the sensation is accompanied by a compulsion to act. For instance, an itch is accompanied by a need to scratch, and a painful stimulus makes us want to withdraw from the pain.

The axons of the tract cells cross over (decussate) to the other side of the spinal cord via the anterior white commissure, and to the anterolateral corner of the spinal cord (hence the spinothalamic tract being part of the anterolateral system). The axons travel up the length of the spinal cord into the brainstem. Pain travels through spinothalamic tracts, and crosses over in the spinal cord at the point it enters, and then travels up contralaterally.

Traveling up the brainstem, the tract moves dorsally. The neurons ultimately synapse with third-order neurons in several nuclei of the thalamus -- including the medial dorsal, ventral posterior lateral, and ventral medial posterior nuclei. From there, signals go to the cingulate cortex, the primary somatosensory cortex, and insular cortex respectively.